Structure of the neurovasculature

An image depicting the cellular structure of the blood vessels in the brain.

Vascular segmentation

An image depicting the cellular segmentation of a blood vessel in the brain

Blood Brain Barrier project - study design

  • 20 cases + 20 controls post-mortem human brain tissue
  • Fancy new method from Oxford collaborators to separate parenchyma and vascular fractions from brain tissue (80 samples total) > single cell seq (10X)

A cartoon deliniating the parenchyma and vascular components of the brain

Data processing

  • Using scFlow
  • Standardised single cell seq pipeline written in Nextflow by Nathan Skene Lab
  • Aspirational goal for informatic pipelines in general for DRI
  • It’s neat though, promise
  • Data will be on ADDI platform, with code and pipeline available for use

UMAP

UMAP with annotated celltypes

UMAP plot coloured by parenchymal or vascular fraction.

AD risk

Pseudobulk

Number of pseudobulk DEGs
celltype Up Down
Astro 223 116
Endothelial 16 2
Microglia 72 71
mystery-cluster 23 5
Neuron-ex 94 87
Neuron-in 67 37
Oligo 218 65
OPC 20 7
Pericyte 62 14

Next project

  • BHF grant - building a vascular atlas
  • 5 regions from 60 post-mortem brains
    • 20 with severe SVD, 20 none/mil/moderate SVD and 20 sudden death controls
    • Same 2 vascular/parenchymal fractions = 600 samples for sequencing
  • Subset of samples for ATACseq and spatial transcriptomics

References

Cardiff DRI CDC talk - 2024-09-30 - Gabriel Mateus Bernardo Harrington

Schaeffer, Samantha, and Costantino Iadecola. 2021. “Revisiting the Neurovascular Unit.” Nature Neuroscience 24 (9): 1198–1209. https://doi.org/10.1038/s41593-021-00904-7.
Warren, Katherine Elizabeth. 2018. “Beyond the Blood:Brain Barrier: The Importance of Central Nervous System (CNS) Pharmacokinetics for the Treatment of CNS Tumors, Including Diffuse Intrinsic Pontine Glioma.” Frontiers in Oncology 8.